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40 results on '"Park, J.R."'

8. Age-dependency of the prognostic impact of tumor genomics in localized resectable MYCN non-amplified neuroblastomas Report from the SIOPEN Biology Group on the LNESG Trials

Author

Ambros, I.M., Tonini, G.P., Gross, N., Mosseri, V., Pötschger, U., Beiske, K., Berbegall, A.P., Bénard, J., Bown, N., Caron, H., Combaret, V., Couturier, J., Defferrari, R., Delattre, O., Jeison, M., Kogner, P., Lunec, J., Marques, B., Martinsson, T., Mazzocco, K., Noguera, R., Schleiermacher, G., Valent, A., Van Roy, N., Villamon, E., Janousek, D., Pribill, I., Glogova, E., Attiyeh, E.F., Hogarty, M.D., Monclair, T., Holmes, K., Valteau-Couanet, D., Pearson ADJ, A.D.J., Castel, V., Tweddle, D.A., Park, J.R., Cohn, S., Ladenstein, R., Beck-Popovic, M., De Bernardi, B., Michon, J., and Ambros, P.F.

Subjects
Neuroblastoma, Tumor Genomics, MYCN, Doenças Genéticas
Abstract

BACKGROUND: Biology based treatment reduction, i.e. surgery alone also in case of not totally resected tumors, was advised in neuroblastoma patients with localized resectable disease without MYCN amplification. However, whether the genomic background of these tumors may influence outcome was unknown and therefore scrutinized in a meta-analysis comprising two prospective therapy studies and a ‘validation’ cohort. PATIENTS AND METHODS: Diagnostic samples were derived from 406 INSS stages 1/2A/2B tumors from three cohorts: LNESGI/II and COG. Genomic data were analyzed in two age groups (cut-off: 18 months) and quality controlled by the SIOPEN Biology Group. RESULTS: In both patient age groups stage 2 tumors led to similarly reduced event-free survival (5y-EFS: 83+3% versus 80+4%), but overall survival was only decreased in patients >18m (5y-OS: 97+1% versus 87+4%; p=0.001). In the latter age subgroup, only tumors with SCA led to relapses, with 11q loss as the strongest marker (5y-EFS: 40+15% versus 89+5%; p18m but not

Published
2018

9. Role of Radiotherapy Dose-Escalation for High-Risk Neuroblastoma with Post-Surgical Primary Site Gross Residual Disease: A Report from the COG ANBL0532 Study

Author

Liu, K.X., primary, Naranjo, A., additional, Zhang, F.F., additional, Dubois, S.G., additional, Braunstein, S.E., additional, Voss, S.D., additional, Khanna, G., additional, London, W.B., additional, Doski, J., additional, Geiger, J., additional, Grupp, S.A., additional, Diller, L.R., additional, Park, J.R., additional, and Haas-Kogan, D.A., additional

Published
2019
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14. SIOP-PODC adapted risk stratification and treatment guidelines: Recommendations for neuroblastoma in low- and middle-income settings

Author

Parikh, N.S., Howard, S.C., Chantada, G., Israels, T., Khattab, M., Alcasabas, P., Lam, C.G., Faulkner, L., Park, J.R., London, W.B., Matthay, K.K., CCA - Innovative therapy, Pediatric surgery, and CCA - Cancer Treatment and quality of life

Abstract

© 2015 The Authors.Neuroblastoma is the most common extracranial solid tumor in childhood in high-income countries (HIC), where consistent treatment approaches based on clinical and tumor biological risk stratification have steadily improved outcomes. Howe

Published
2015

17. Extent of Lymph Node Radiation Coverage in High-Risk Neuroblastoma Does Not Affect Clinical Outcome: A Report From the COG A3973 Study

Author

Haas-Kogan, D., primary, Douglas, J., additional, London, W.B., additional, McCauley Van Ryn, C.J., additional, von Allmen, D., additional, Davidoff, A.M., additional, Villablanca, J.G., additional, Matthay, K.K., additional, DuBois, S.G., additional, Kreissman, S.G., additional, La Quaglia, M.P., additional, and Park, J.R., additional

Published
2014
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31. Why promising technologies fail: the neglected tole of user innovation during adoption

Author

Douthwaite, B., Keatinge, J.D.H., and Park, J.R.

Subjects
Technological innovations -- Social aspects, Business, Business, general, Social sciences
Abstract

A new study analyses where traditional research and development approaches are most likely to have the greatest impact and why user innovation is crucial during adoption. Case studies of farming systems in Asia are included.

Published
2001

32. Characteristics of Low- k Nanoporous Poly(methylsilsequioxane) Thin Films.

Author

Sung-Kyu Min, J.R., Jae-Man Park, J.R., KItae Song, J.R., Moon Young Jin, J.R., Changjin Lee, J.R., Do Yeung Yoon, J.R., and Hee-Woo Rhee, J.R.

Subjects
*PHYSICAL constants, *DIELECTRICS, *THIN films
Abstract

Nanoporous poly(methyl silsesquioxane) (PMSSQ) was obtained by sintering organic/inorganic nanohybrids. The porogen was cyclosiloxane with four poly(ethylene glycol) arms for better miscibility with PMSSQ. As the porogen content in the hybrid increased up to 30 vol%, the porosity of the calcined PMSSQ film increased up to 24%, and the k values decreased as low as 2.12. However, the interconnected pore structure was observed at the porogen content above 25 vol%. The miscibility was improved compared to poly(caprolactone)-based porogens and the pore size was indistinguishable even at SEM resolution. [ABSTRACT FROM AUTHOR]

Published
2002
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38. Accelerating drug development for neuroblastoma: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma

Author

Moreno, Lucas, Barone, Giuseppe, DuBois, Steven G, Molenaar, Jan, Fischer, Matthias, Schulte, Johannes, Eggert, Angelika, Schleiermacher, Gudrun, Speleman, Frank, Chesler, Louis, Geoerger, Birgit, Hogarty, Michael D, Irwin, Meredith S, Bird, Nick, Blanchard, Guy B, Buckland, Sean, Caron, Hubert, Davis, Susan, De Wilde, Bram, Deubzer, Hedwig E, Dolman, Emmy, Eilers, Martin, George, Rani E, George, Sally, Jaroslav, Štěrba, Maris, John M, Marshall, Lynley, Merchant, Melinda, Mortimer, Peter, Owens, Cormac, Philpott, Anna, Poon, Evon, Shay, Jerry W, Tonelli, Roberto, Valteau-Couanet, Dominique, Vassal, Gilles, Park, Julie R, Pearson, Andrew D J, UU BETA RESEARCH, Blanchard, Guy [0000-0002-3689-0522], Philpott, Anna [0000-0003-3789-2463], Apollo - University of Cambridge Repository, UU BETA RESEARCH, Moreno L., Barone G., DuBois S.G., Molenaar J., Fischer M., Schulte J., Eggert A., Schleiermacher G., Speleman F., Chesler L., Geoerger B., Hogarty M.D., Irwin M.S., Bird N., Blanchard G.B., Buckland S., Caron H., Davis S., De Wilde B., Deubzer H.E., Dolman E., Eilers M., George R.E., George S., Jaroslav, Maris J.M., Marshall L., Merchant M., Mortimer P., Owens C., Philpott A., Poon E., Shay J.W., Tonelli R., Valteau-Couanet D., Vassal G., Park J.R., and Pearson A.D.J.

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Drug development, Antineoplastic Agents, Medical Oncology, Pediatrics, 03 medical and health sciences, Neuroblastoma, 0302 clinical medicine, Clinical trials, Phase I, Drug Development, Internal medicine, MYCN, Drug Discovery, medicine, Anaplastic lymphoma kinase, Humans, Molecular Targeted Therapy, Child, Protein Kinase Inhibitors, ATRX, Drug discovery, business.industry, Paediatric oncology, Brain Neoplasms, Therapies, Investigational, Epigenetic, Cancer, Preclinical testing, Congresses as Topic, medicine.disease, 3. Good health, Clinical trial, Europe, 030104 developmental biology, 030220 oncology & carcinogenesis, Epigenetics, business
Abstract

Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 to accelerate the development of new drugs for neuroblastoma. Advances have occurred, with eight of nine high-priority targets being evaluated in paediatric trials including anaplastic lymphoma kinase inhibitors being investigated in front-line, but significant challenges remain. This article reports the conclusions of the second NDDS forum, which expanded across the Atlantic to further develop the initiative. Pre-clinical and clinical data for 40 genetic targets and mechanisms of action were prioritised and drugs were identified for early-phase trials. Strategies to develop drugs targeting TERT, telomere maintenance, ATRX, alternative lengthening of telomeres (ALT), BRIP1 and RRM2 as well as direct targeting of MYCN are high priority and should be championed for drug discovery. Promising pre-clinical data suggest that targeting of ALT by ATM or PARP inhibition may be potential strategies. Drugs targeting CDK2/9, CDK7, ATR and telomere maintenance should enter paediatric clinical development rapidly. Optimising the response to anti-GD2 by combinations with chemotherapy, targeted agents and other immunological targets are crucial. Delivering this strategy in the face of small patient cohorts, genomically defined subpopulations and a large number of permutations of combination trials, demands even greater international collaboration. In conclusion, the NDDS provides an internationally agreed, biologically driven selection of prioritised genetic targets and drugs. Improvements in the strategy for conducting trials in neuroblastoma will accelerate bringing these new drugs more rapidly to front-line therapy. (C) 2020 Elsevier Ltd. All rights reserved.

Published
2020

40. Ischemia-Selective Cardioprotection by Malonate for Ischemia/Reperfusion Injury.

Author

Prag HA, Aksentijevic D, Dannhorn A, Giles AV, Mulvey JF, Sauchanka O, Du L, Bates G, Reinhold J, Kula-Alwar D, Xu Z, Pellerin L, Goodwin RJA, Murphy MP, and Krieg T

Subjects
Animals, Chromatography, Liquid, HeLa Cells, Humans, Ischemia, Malonates pharmacology, Malonates therapeutic use, Mice, Mice, Inbred C57BL, Myocytes, Cardiac, Tandem Mass Spectrometry, Myocardial Reperfusion Injury drug therapy, Myocardial Reperfusion Injury prevention & control
Abstract

Background: Inhibiting SDH (succinate dehydrogenase), with the competitive inhibitor malonate, has shown promise in ameliorating ischemia/reperfusion injury. However, key for translation to the clinic is understanding the mechanism of malonate entry into cells to enable inhibition of SDH, its mitochondrial target, as malonate itself poorly permeates cellular membranes. The possibility of malonate selectively entering the at-risk heart tissue on reperfusion, however, remains unexplored., Methods: C57BL/6J mice, C2C12 and H9c2 myoblasts, and HeLa cells were used to elucidate the mechanism of selective malonate uptake into the ischemic heart upon reperfusion. Cells were treated with malonate while varying pH or together with transport inhibitors. Mouse hearts were either perfused ex vivo (Langendorff) or subjected to in vivo left anterior descending coronary artery ligation as models of ischemia/reperfusion injury. Succinate and malonate levels were assessed by liquid chromatography-tandem mass spectrometry LC-MS/MS, in vivo by mass spectrometry imaging, and infarct size by TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining., Results: Malonate was robustly protective against cardiac ischemia/reperfusion injury, but only if administered at reperfusion and not when infused before ischemia. The extent of malonate uptake into the heart was proportional to the duration of ischemia. Malonate entry into cardiomyocytes in vivo and in vitro was dramatically increased at the low pH (≈6.5) associated with ischemia. This increased uptake of malonate was blocked by selective inhibition of MCT1 (monocarboxylate transporter 1). Reperfusion of the ischemic heart region with malonate led to selective SDH inhibition in the at-risk region. Acid-formulation greatly enhances the cardioprotective potency of malonate., Conclusions: Cardioprotection by malonate is dependent on its entry into cardiomyocytes. This is facilitated by the local decrease in pH that occurs during ischemia, leading to its selective uptake upon reperfusion into the at-risk tissue, via MCT1. Thus, malonate's preferential uptake in reperfused tissue means it is an at-risk tissue-selective drug that protects against cardiac ischemia/reperfusion injury.

Published
2022
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